Relationship among Age, Education and Frailty in Older Persons.

Preliminary data suggest that frailty tend to increase with age and is associated with fewer years of formal education. However, it is still unclear whether age and education synergistically act in the definition of frailty. Aim of the study is to evaluate the interaction between age and education in defining frailty in community-dwelling older persons. We considered 911 community-dwelling older adults (mean age 79.5 years) who underwent a comprehensive geriatric assessment. Our results showed that education and age interact in the definition of frailty following an exponential-type relationship. Whereas age is a non-modifiable risk factor, much can be done to address the social component of frailty here represented by education. The reported interaction suggests that social interventions might be particularly effective at an older age, paving the way for multidisciplinary interventions beyond the clinical field.

Frailty and Persistent Pain in Oncological Patients Undergoing Rehabilitation.

OBJECTIVES: Pain is one of the most common symptoms among oncological patients and has a strong negative impact on quality of life. The aim of this study is to assess if frailty and polypharmacy are associated with persistent pain in oncological patients undergoing rehabilitation. DESIGN: Observational, prospective, longitudinal study. SETTING AND PARTICIPANTS: Data are from oncological patients admitted to the Oncological Rehabilitation Unit. METHODS: Presence of pain, its intensity and characteristics were evaluated at the admission and after 7 days. A Frailty Index (FI) was computed from Comprehensive Geriatric Assessment (CGA) data. RESULTS: Among the 45 consecutively recruited patients (mean age 72 years, woman 44%), pain was present in 20 (44%) patients at the admission and 9 (20%) after 7 days of stay. Forty-one patients (92%) were taking more than 5 drugs at the admission (mean 9 drugs). The FI was normally distributed and descriptive statistics define our population as frail (mean 0.44; range 0.23-0.64). The FI was significantly associated with the presence of pain (OR 2.66; 95%CI 1.13-6.27, p=0.03) and its intensity after 7 days from the admission (ß 4.24 95% CI 1.28 - 7.19, p=0.006), even after adjustment for potential confounders. CONCLUSIONS AND IMPLICATIONS: Investigating frailty in cancer patients to implement multidisciplinary strategies could play an important role in improving persistent pain.

Low levels of LTB4 in cerebrospinal fluid of AIDS patients with cryptococcal meningitis.

In this study we evaluated the release of leukotriene B4 (LTB4) in the cerebrospinal fluid (CSF) of 12 patients with Acquired Immunodeficiency Syndrome (AIDS), which disease was complicated by Cryptococcal Meninigitis and in CSF of 12 control subjects with inflammatory and degenerative pathologies of the Central Nervous System (CNS). We obtained low levels of LTB4 in all the AIDS patients (mean 60.5 pg/ml), while the HIV negative subjects with degenerative and inflammatory pathologies of CNS showed a mean of 91.5 pg/ml. The finding of low levels of this inflammatory reaction mediator agrees with the limited clinical symptoms of cryptococcal meningoencephalitis in patients affected by AIDS.

Mediator release in cerebrospinal fluid of human immunodeficiency virus-positive patients with central nervous system involvement.

In this study we evaluated the release of some mediators of inflammatory reactions such as histamine (H), leukotriene B4 (LTB4), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in the cerebrospinal fluid (CSF) of 15 patients with acquired immunodeficiency syndrome (AIDS), eight with opportunistic infections of the central nervous system (CNS) and seven without HIV-related neurological pathology, and of 25 HIV-negative control subjects with other neurological diseases. The cerebrospinal LTB4 level was increased in all the AIDS patients (mean 348 pg/ml); the control group revealed normal levels of LTB4 in the CSF (mean 63.2 pg/ml). The PGD2 level in the HIV-positive (mean 264 pg/ml) patients was higher than of the control subjects (mean 50 pg/ml), while low LTC4 levels were found both in the HIV-positive and control groups. We did not find any significant concentration of H in the CSF of either the HIV-positive or the control subjects. These findings may be due to the presence of chronic HIV infection or to the opportunistic infections of the CNS that so often occur in the latest stages of the disease.

Enhanced basophil releasability in subjects infected with human immunodeficiency virus.

Spontaneous histamine release and basophil response to IgE-dependent (anti-IgE) and IgE-independent (formyl-methionine peptide, calcium ionophore A23187) stimuli were evaluated in 15 patients with acquired immunodeficiency syndrome (AIDS), 8 with AIDS related complex (ARC), 7 with lymphadenopathy syndrome (LAS), 11 seropositive asymptomatic subjects, 10 human immunodeficiency virus (HIV)-seronegative drug addicts, and 20 normal subjects. Both spontaneous histamine release and anti-IgE-induced histamine release were significantly increased in HIV-infected subjects, in comparison with seronegative drug addicts and normal controls. Basophil response to anti-IgE was higher in AIDS/ARC patients than in seropositive asymptomatic subjects and LAS patients, although the difference was not statistically significant. When basophils were challenged with 0.1 microM formyl-methionine peptide, a significantly increased histamine secretion was found in HIV-infected subjects; conversely, at the higher formyl-methionine peptide concentration (10 microM), as well as at all calcium ionophore A23187 concentrations, histamine release was similar in all the studied groups. No correlation was found among anti-IgE-induced histamine release, total lymphocyte counts, CD4+ and CD8+ T cell counts, and total serum IgE levels. These findings indicate that infection with HIV is associated with an increased basophil releasability. This could be of some relevance in the increased incidence of allergic manifestations and adverse drug reactions observed in AIDS patients.

[The inflammatory process]. / Il processo infiammatorio.

Foremost among the various mechanisms which have developed during the evolution of living creatures are those taking place during the inflammatory process, triggering defense mechanisms vs. chemical, physical and biological toxic agents. The present review aims at explaining some of the physiopathological mechanisms which play a role during inflammation.

Anti-endothelial cell antibodies in patients with Wegener's granulomatosis and micropolyarteritis.

Anti-endothelial cell antibodies (AECA) have been detected by cell surface radioimmunoassay in nine out of 15 patients with micropolyarteritis (MPA) and in two out of five patients with Wegener's granulomatosis. AECA mostly belonged to the IgG isotype and were present in the active phase of the diseases. These antibodies were not detectable in 10 sera from patients with essential mixed cryoglobulinaemia, suggesting that they were not a mere epiphenomenon consequent to the inflammatory vascular injury. The binding activity was not related to ABH antigens or to HLA class I antigens displayed by resting human endothelial cells in culture and was not influenced by removing immune complexes. Absorption of the anti-neutrophil cytoplasmic antibodies (ANCA), present in MPA and Wegener's granulomatosis sera, did not affect the endothelial binding. AECA-positive sera did not display lytic activity against endothelial cells, neither alone nor after addition of fresh complement or normal human peripheral blood mononuclear cells. Although AECA are not cytolytic for endothelial cell monolayers in vitro, the reactivity against intact endothelial cells suggests their possible involvement in in vivo pathological processes affecting vascular structures in small vessel primary vasculitides.

A trial with ribavirin in patients with AIDS or AIDS-related complex.

A therapeutic trial is described which concerns 6 patients with AIDS and 6 patients with ARC who were submitted to a 6 month course of Ribavirin. Ribavirin was administered orally as the following doses: 3.000 mg daily the first week, 2.000 mg daily the second 2 weeks, and 1.000 mg daily up to completion of the 6 months period. No major side-effects were recorded; only a transient anemia was observed in almost all patients at the higher dose; none of them, however, required to be transfused. No improvement was shown by any of the 6 AIDS patients, neither clinically nor according to laboratory test, whereas all 6 patients with ARC experienced a sense of well-being, a clearing of their symptoms and an average weight gain of about 2.5 kg. No significant changes, though, were recorded as for their immune parameters. A remarkable drop of aminotransfereas was also observed in 4 of the patients, who were affected with chronic hepatitis as well. We conclude that additional, if any, Ribavirin trials should be carried out only in ARC patients.

Activity of substance P on human skin and nasal airways.

Nasal challenge and intradermal injection with substance P (SP) were performed in five normal subjects and in five patients suffering from allergic rhinitis. No clinical symptoms, local histamine release, or modifications of nasal airway resistance were observed when SP was insufflated in the nose. Conversely, intradermal injection with SP caused a wheal and flare reaction in all the studied subjects. The different response to SP is likely to be due to the heterogeneity of human skin and nasal mucosa mast cells as far as sensitivity to histamine-releasing agents is concerned. Our findings indicate that SP has no relevant effect on human nasal mucosa, even if a synergetic action of SP with other allergic mediators cannot be excluded. The role of SP in the pathogenesis of allergic diseases in humans remains to be defined and deserves further study.

Study of the effect of some neuropeptides and endogenous opioid peptides on in vitro histamine release from human lung mast cells and peripheral blood basophils.

In the present study we investigated the effect of substance P, bombesin, beta lipotropin, alpha and gamma endorphins, and metionin and leucin enkephalins on in vitro histamine release from partially purified human lung mast cells and peripheral blood basophils. In the concentration range of 10-100 microM, these neuropeptides and endogenous opioid peptides neither elicited a significant histamine secretions from human lung mast cells and blood basophils, nor influenced the anti-IgE-induced histamine release. These data indicate that human lung mast cells and blood basophils are resistant to the activity of substance P, bombesin, beta lipotropin, alpha and gamma endorphins, and metionin and leucin enkephalins, and confirm the functional heterogeneity of mast cells, depending on the species and the tissue origin.

Cord blood basophil releasability: a predictive marker for allergy?

Liberation of histamine and LTC4 by cord-blood basophils was measured in the newborn from healthy and atopic parents. The cord-blood basophils of the second classification produced more histamine than those from the first, after challenge with anti-IgE. Thus, a newborn from atopic parent(s) probably carries more fixed IgE on the basophils than a newborn from healthy parents and so the capacity of cord-blood basophils to liberate mediators may be a good marker of allergy.

Cord blood basophil releasability: evaluation of histamine release and leukotriene C4 generation.

This study was performed to evaluate mediator (histamine and leukotriene C4) release from cord blood and adult blood basophils, challenged with IgE-independent (calcium ionophore A23187) and IgE-mediated (anti-IgE) stimuli. IgE-independent mediator release was similar in adult blood and umbilical blood basophils. Conversely, the anti-IgE-induced histamine and immunoreactive leukotriene C4 (iLTC4) release was significantly reduced in cord blood basophils. Passive sensitization with an IgE-rich serum was followed by a significant increase in the number of eluted IgE molecules from cord blood basophils and by an increase in IgE-mediated histamine release. iLTC4 production was not affected by passive sensitization of umbilical blood basophils. The IgE-dependent mediator release from cord blood basophils was not correlated with the number of cell-bound IgE. In addition, histamine secretion and leukotriene C4 production from cord blood basophils seem to be independent events.

Mediators and allergic inflammation of human airways.

Local antigen challenge in patients with respiratory allergy is associated with histamine and arachidonic acid metabolites release, both in upper and in lower respiratory airways. Raised histamine levels can be detected in nasal secretions 5 min after allergen stimulation. Increased leukotriene C4 and prostaglandin D2 concentrations persist for a longer period (respectively 20 and 30 min). Endobronchial antigen stimulation is also followed by release of histamine, leukotriene C4 and prostaglandin D2, which can be detected in bronchial lavage fluid. Elevated concentrations of these mediators can be found 5 and 15 min after challenge. Moreover, endobronchial antigen stimulation is associated with an increase in the number of bronchial epithelial cells recovered in bronchial lavage fluids.

Effects of silybin on histamine release from human basophil leucocytes.

1. Effects of a naturally occurring flavonoid, silybin, on histamine release from human basophils were examined, in order to assess the potential utility in the treatment of allergic disorders. 2. The f-met peptide and anti-IgE-induced histamine release was significantly (P less than 0.05) inhibited in a concentration-dependent fashion. Conversely, no significant (P greater than 0.05) effect on calcium ionophore A23187-induced histamine secretion was documented. The inhibitory activity was significantly (P less than 0.05) reversed by elevating extracellular calcium concentrations. 3. The anti-allergic properties of silybin can be reasonably ascribed to a membrane-stabilizing activity, possibly related to an interference in calcium influx. These results indicate that an in vivo evaluation of the anti-allergic activity of silybin would be worthwhile.

The role of suggestion in asthma. I. Effects of inactive solution on bronchial reactivity under bronchoconstrictor or bronchodilator suggestion.

Twenty-eight subjects affected by perennial asthma were selected in order to investigate the possibility of inducing or relieving an asthmatic attack by means of suggestion. Twenty-five were positive to methacholine challenge test and, among them, eleven reacted to an ultrasonic nebulized distilled water test. The effect of suggestion on airway response was assessed by eight inhalations of normal saline at 32 degrees C alternately presented as a bronchoconstrictor or as a bronchodilator drug. Eight inhalations of the same diluent without any psychic stimulus were used as control test. Seven patients reacted with bronchoconstriction to both positive and negative suggestion and to control test. Further, this group of patients showed a lower methacholine PD20 when compared with the other subjects. In this study, the effects of suggestion on bronchial reactivity were not observed and bronchoconstriction belonged to an individual hyperreactivity of the airways.

Behavior and clinical relevance of histamine and leukotrienes C4 and B4 in grass pollen-induced rhinitis.

The release kinetics of histamine and leukotrienes C4 (LTC4) and B4 (LTB4) were investigated in nasal secretions of 10 patients with hay fever after antigen challenge. High levels of biologically active histamine were found in nasal washes from asymptomatic allergic and normal subjects. With repeated lavages, the amount of histamine recovered dropped markedly. Grass pollen challenge was followed by a significant (p less than 0.05) dose-dependent and time-limited (5 min) increase in histamine level in 7 of 10 patients; these values, however, were lower than those found in basal conditions. In 8 of 10 patients with hay fever, antigen challenge induced a significant (p less than 0.05) dose-dependent increase in LTC4 level, which persisted for 30 min. The LTC4 generation was well correlated with the appearance of allergic symptoms; LTB4 production was found in 2 patients only. A different pattern of symptoms was observed after in vivo nasal stimulation with histamine and LTC4. Histamine caused sneezing, itching, rhinorrhea, and nasal obstruction; conversely, the main symptom induced by LTC4 was a more pronounced and longer lasting nasal obstruction.

Effect of nitrendipine on histamine release from human basophil leukocytes.

The effect of the new calcium antagonist nitrendipine on in vitro basophil activation was evaluated in 10 subjects. The histamine release induced by calcium ionophore A23187, f-met peptide and anti-IgE was inhibited, in a dose-dependent fashion, by nitrendipine in the concentration range of 1-100 microM. The activity of this calcium antagonist seems complex and related to an interference with calcium at multiple sites. At concentrations higher than 200 microM, nitrendipine causes histamine release from basophil leukocytes. This histamine secretion is likely to be due to a cytotoxic effect, since it is associated with an increase in LDH levels in the cell supernatant.

Effect of calcium antagonists on histamine release from human basophil leukocytes.

The effect of calcium antagonists on basophil activation was investigated in 14 subjects. Verapamil, methoxyverapamil and diltiazem, in a concentration range of 1-100 microM, exert a concentration-dependent inhibition on the human basophil histamine release induced by calcium ionophore A23187, zymosan activated human serum and grass pollen allergens. This inhibitory effect is highly variable from subject to subject and from drug to drug. At concentrations higher than 200 microM, verapamil, methoxyverapamil and diltiazem induce a calcium independent histamine secretion from basophil leukocytes. This mediator release is associated with an increase in LDH levels in the cell supernatant and seems to be due to a cytotoxic effect.

Functional evaluation of the basophil/IgE system in the cord blood.

Basophil releasability was studied in 24 cord blood samples from normal-term deliveries. The histamine content in cord blood basophils was similar to that of adult blood basophils. The response to IgE-independent degranulating stimuli such as calcium ionophore A23187 and zymosan-activated human serum was overlapping with that of normal adults. Conversely, a reduced releasability was observed after challenge with anti-IgE, even after sensitization with an IgE-rich serum. The IgE-dependent degranulation seems to be hampered by the low concentrations of circulating and cell-bound IgE antibodies. The number of IgE molecules bound to the specific receptors in cord blood basophils is significantly lower than in adult blood basophils.

Evaluation of allergic etiology in perennial rhinitis.

In 197 patients with perennial rhinitis, 49 patients (24.9%) were found to be allergic to perennial inhalant allergens, 37 patients (18.8%) allergic to seasonal allergens, 52 patients (26.4%) had food intolerance, 12 patients (6.6%) showed evidence of nasal infection, and in 46 patients (23.3%) etiology was undetermined.